Trial Information

Phase I Trial With Cohort Expansion of Pentostatin, Bendamustine and Ofatumumab (PBO) for the Treatment of Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. There has been considerable progress in understanding the biology and treatment of CLL in the last 20 years. However, even with modern therapies, complete responses (CR) are achieved in approximately 25% of the patients with relapsed/refractory disease. Multiple studies have demonstrated that patients who achieve CR have better clinical outcomes than patients who do not achieve a CR with therapy. B-cell NHL is composed of multiple subtypes of neoplasm. These diseases are closely related to CLL in terms of natural history, biology, and responsiveness to similar therapeutic agents. These diseases are not usually cured by available chemotherapy and ultimately patients succumb to progression of resistant disease. Therefore, there is a need to develop better therapies to improve survival in patients with CLL and B-cell NHL.

Preclinical and clinical data suggests that pentostatin, bendamustine, ofatumumab are active drugs for the treatment of B-cell malignancies. In an earlier clinical trial conducted by Dr. Weiss (lead site PI), the combination of pentostatin and cyclophosphamide had very good activity in previously treated patients with B-cell neoplasms. This regimen was also better tolerated than similar fludarabine-based regimen. The response rates were improved with addition of rituximab, anti CD 20 antibody, to the above regimen. Studies have demonstrated synergy between bendamustine and purine analogs like pentostatin in killing cancer cell types of CLL and NHL. The combination of these three drugs (pentostatin, bendamustine and ofatumumab) has not been tested in clinical setting and we anticipate that the combination regimen will be more active than individual drugs alone. The aim of this trial is to find a safe dose of bendamustine to be used in combination with pentostatin and ofatumumab in patients with previously treated CLL and B-cell NHL.

9. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.

10. Positive serology for hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.

11. Active hepatitis C infection. If positive serology for hepatitis C (HC) defined as a positive test for HCAb, HC quantitative PCR will be performed. If PCR is positive the subject will be excluded

12. Screening laboratory values:

1. creatinine > 2.0 times upper normal limit and creatinine clearance < 30 ml/min/m2. Patients with creatinine > 2 times upper limit of normal will have creatinine clearance estimated. At the discretion of treating physician, creatinine clearance can be measured and that value can be used instead of calculated creatinine clearance.

2. total bilirubin > 2 times upper normal limit (unless due to tumor involvement of liver or a known history of Gilbert's disease)

13. Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening.

14. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.

15. Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy

Type of Study:

Study Design:

Outcome Measure:

Maximum Tolerated Dose (MTD) of Bendamustine

Outcome Description:

The primary objective of this study is to determine the dose of bendamustine in combination with pentostatin and ofatumumab at which <33% of patients with relapsed Non-Hodgkin's Lymphoma (NHL) or Chronic Lymphocytic Leukemia (CLL) experience severe toxicity; and to assess the toxicity of this regimen.

Outcome Time Frame:

Up to 6 months

Safety Issue:

Yes

Principal Investigator

Mark Weiss, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Thomas Jefferson University

Authority:

United States: Institutional Review Board

Study ID:

11P.166

NCT ID:

NCT01352312

Start Date:

May 2011

Completion Date:

June 2015

Related Keywords:

Chronic Lymphocytic Leukemia

B-cell Non-Hodgkin's Lymphoma

Chronic Lymphocytic Leukemia

Non-Hodgkin's Lymphoma

B-cell

leukemia

lymphoma

bendamustine

pentostatin

ofatumumab

NHL

CLL

Leukemia

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Lymphoid

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, B-Cell

Name

Location

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